Hybrid Immune Cells Have Antitumor Effects in Early Stage Lung Cancer

A subset of tumor-associated neutrophils (TANs) has hybrid characteristics of both neutrophils and antigen-presenting cells in samples from early stage human lung cancers. This study is the first to observe this phenomenon in a human tumor.¹

The microenvironment of tumors is a mix of cell types, mostly comprised of inflammatory cells. White blood cells (WBCs) represent a significant portion of these inflammatory cells and influence nearly all steps of tumor progression. Tumor associated neutrophils (TANs), one type of WBC, predominates; however, the role of TANs in tumor development remains largely unexplored in humans.

This research sought to characterize TANs and determine their specific roles in regulating T cell responses in patients with early stage lung cancer. Cytotoxic T lymphocytes are the chief effector cells that mediate antitumor immunity.

“We tried to ascertain the function of this hybrid subset of TANs,” said Evgeniy B. Eruslanov, PhD, a research assistant professor in the Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and senior author on the study. “Are they there to help the tumor grow or to fight its existence? We show that small size, early stage lung tumors can induce the formation of a unique type of tumor-associated cells that can trigger and support antitumor T cell responses, thus potentially limiting the growth of the cancer.”

“Our findings demonstrate that the early stage lung tumor microenvironment can drive neutrophils to differentiate into a cell subset with enhanced antitumor capabilities. Interestingly, this hybrid population disappears as tumors enlarge,” said coauthor Sunil Singhal, MD, of the department of surgery at Perelman. He provided fresh tumor tissue from patients with lung cancer and participated in research.

The authors explained that their findings demonstrate the potential antitumor role of these cells in early stage cancer and may provide opportunities to boost the antitumor efficacy of cytotoxic T cells. An understanding of the cellular and molecular processes in early stage tumors will allow researchers to identify which immune forces need to be augmented to facilitate natural protection against tumor development.

“We want to take advantage of these unique early tumor neutrophils to help them better stimulate the antitumor cytotoxic T cells,” Eruslanov said. “Perhaps if we can expand the hybrid neutrophils in patients early on, we can augment antitumor T cell activity.”

Reference

1. Singhal S, Bhojnagarwala PS, O’Brien S, et al. Origin and role of a subset of tumor-associated neutrophils with antigen-presenting cell features in early-stage human lung cancer. Cancer Cell. 2016;30(1):120-135.